Loss of CD28 expression on T lymphocytes: a marker of replicative senescence.
The CD28 molecule, a disulfide-linked homodimer expressed on peripheral T cells and thymocytes, mediates an essential costimulatory signal following engagement of the T cell receptor (TCR). Increased proportions of CD28- T cells have been observed during aging and in situations of chronic immune stimulation, but the origin and functional characteristics of these cells have been unclear. T cells which reach replicative senescence in culture after multiple rounds of cell division have shortened telomeres, respond poorly to stress stimuli, and no longer express CD28, suggesting that CD28- T cells observed in vivo may be the progeny of memory cells which have been repeatedly stimulated. This review describes the features of T cell replicative senescence, presents several possible mechanisms for the generation of senescent T cells in vivo, and proposes that replicative senescence may explain immune exhaustion.
Effros
R B
RB
Department of Pathology and Laboratory Medicine, UCLA School of Medicine 90095-1732, USA.
D015415:Biomarkers; D018106:CD28 Antigens / Q000096:biosynthesis* / Q000276:immunology; D002455:Cell Division; D016922:Cellular Senescence; D006801:Humans; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D016615:Telomere
D015415:Biomarkers; D018106:CD28 Antigens